Vinblastine → 4-Desacetylvinblastine

HRID 499966

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HRID 499966 반응식
[CH3:1][CH2:2][C@@:3]1([OH:59])[CH2:21][N:19]2[CH2:20][C@H:5]([CH2:6][C@:7]([C:55]([O:57][CH3:58])=[O:56])([C:22]3[CH:23]=[C:24]4[C@:32]56[C@@H:36]7[C@:37]([CH2:52][CH3:53])([C@@H:41]([O:48]C(C)=O)[C@:42]([OH:47])([C:43]([O:45][CH3:46])=[O:44])[C@@H:31]5[N:30]([CH3:54])[C:25]4=[CH:26][C:27]=3[O:28][CH3:29])[CH:38]=[CH:39][CH2:40][N:35]7[CH2:34][CH2:33]6)[C:8]3[NH:16][C:15]4[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=4[C:9]=3[CH2:17][CH2:18]2)[CH2:4]1.CC[C@@]1(O)CN2C[C@H](C[C@](C(OC)=O)(C3C=C4[C@]56[C@@H]7[C@](CC)([C@@H](OC(C)=O)[C@](O)(C(OC)=O)[C@@H]5N(C)C4=CC=3OC)C=CCN7CC6)C3NC4C=CC=CC=4C=3CC2)C1.OS(O)(=O)=O>NN.C(O)C>[CH3:1][CH2:2][C@@:3]1([OH:59])[CH2:21][N:19]2[CH2:20][C@@H:5]([CH2:6][C@:7]([C:55]([O:57][CH3:58])=[O:56])([C:22]3[CH:23]=[C:24]4[C:32]56[C@@H:31]([N:30]([CH3:54])[C:25]4=[CH:26][C:27]=3[O:28][CH3:29])[C@@:42]([OH:47])([C:43]([O:45][CH3:46])=[O:44])[C@H:41]([OH:48])[C@:37]3([CH2:52][CH3:53])[CH:38]=[CH:39][CH2:40][N:35]([C@H:36]53)[CH2:34][CH2:33]6)[C:8]3[NH:16][C:15]4[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=4)[C:9]=3[CH2:17][CH2:18]2)[CH2:4]1

참가 물질

4

반응물 2

HCID 13342VinblastineHCID 5388983Vinblastine Sulfate

생성물 1

HCID 1970264-Desacetylvinblastine

시약·촉매·용매 1

HCID 129679701Hydrazine-ethanol용매

실험 절차

Vinca alkaloids such as vinblastine can be conjugated directly to aldehyde-bearing linkers following conversion to a hydrazide form as described by Brady et al. (J. Med. Chem., 45:4706-4715, 2002). Briefly, vinblastine sulfate is dissolved in 1:1 hydrazine/ethanol and heated to 60° C.-65° C. for 22 hours to yield desacetylvinblastine 3-carboxhydrazide (Table 2, DAVCH). Alternatively, amine-reactive forms of vinblastine may be generated in situ as described by Trouet et al. (U.S. Pat. No. 4,870,162) by (1) initially converting vinblastine sulfate to the desacetyl form (e.g. as described by Brady et al., reacting with 1:3 hydrazine/methanol at 20° C. for 20 hours), (2) reacting the resulting free base with approximately 2-fold excess succinic anhydride to generate the hemisuccinate (Table 2, DAVS), and (3) reacting with isobutyl chloroformate to form the reactive mixed anhydride.

후처리

  1. temperatureheated to 60° C.-65° C. for 22 hours

출처 및 근거

ORD 기록
ord-a46daf678c7e43fd939a5eee01069ad7
출처 데이터셋
uspto-grants-2010_08
특허 번호
US07767803B2

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